The Art and Science of Microencapsulation
What do scratch-and-sniff perfume advertisements, laundry detergents, baking mixes, and aspirin have in common? Each product relies on microencapsulation to provide its unique attributes. Microencapsulation is a process by which tiny parcels of a gas, liquid, or solid active ingredient are packaged within a second material for the purpose of shielding the active ingredient from the surrounding environment. These capsules, which range in size from one micron (one-thousandth of a millimeter) to seven millimeters, release their contents at a later time by means appropriate to the application.
There are four typical mechanisms by which the core material is released from a microcapsule mechanical rupture of the capsule wall, dissolution of the wall, melting of the wall, and diffusion through the wall. Less common release mechanisms include ablation (slow erosion of the shell) and biodegradation.
Two well-known applications of microencapsulated products rely on mechanical rupture of the shell to release the core contents. Scratch-and-sniff perfume advertisements work because tiny perfume-filled microcapsules are coated onto the magazine page. When scratched, the shell wall ruptures, releasing the perfume. Carbonless copy paper utilizes the same release mechanism. Small capsules, 120 microns in diameter, coat the underside of the top sheet of paper. The capsules contain a dye precursor a clear chemical that by itself will not put a mark on the lower page, but darkens in color when exposed to an acidic component (such as attapulgite clay or phenolic resin). This acidic component coats the top of the lower sheet. When subjected to the high local pressure beneath a pen point, the capsules break, the two reactants mix, and the copy appears on the lower sheet.
Another area where microencapsulation has been widely applied is in the detergent industry. Some powder detergents contain protein reactive enzymes such as protease, used in removing blood stains. The enzymes are encapsulated in a water-soluble polymer, such as polyethylene glycol, for aesthetic reasons and safe handling purposes. Released upon shell dissolution in the washing machine, the enzymes attack the blood protein, thereby helping to remove the blood stain.
Many packaged baking mixes include encapsulated ingredients to delay chemical reactions until proper temperatures are reached. Sodium bicarbonate is a baking ingredient that reacts with food acids to produce leavening agents, which give baked goods their volume and lightness of texture. To delay and control the leavening process, the sodium bicarbonate is encapsulated in a fat, which is solid at room temperature but melts at a temperature of about 125° F. Release of the core material is delayed until the proper temperature is reached.
Microencapsulated products in the pharmaceutical industry are common, particularly when sustained release of a medication is required. Aspirin provides effective relief for fever, inflammation, and arthritis, but direct doses of aspirin can cause peptic ulcers and bleeding. The drug is therefore sometimes encapsulated in ethyl cellulose or hydroxypropyl methylcellulose and starch (aspirin tablets are formed by pressing together collections of these microcapsules). Rather than being released all at once, the aspirin diffuses through the shell in a slow, sustained dose.
Microencapsulation is a growing field that is finding application in many technological disciplines. A wide range of core materials in addition to those listed above have been encapsulated. These include adhesives, agrochemicals, catalysts, living cells, flavor oils, pharmaceuticals, vitamins, and water. There are many advantages to microencapsulation. Liquids can be handled as solids, odor or taste can be effectively masked in a food product, core substances can be protected from the deleterious effects of the surrounding environment, toxic materials can be safely handled, and drug delivery can be controlled and targeted. In most microcapsules, the shell materials are usually organic polymers; however, waxes and fats have also been used, particularly in food and drug applications where the shell must meet U.S. Food and Drug Administration specifications.
Microencapsulation as an Art
The preparation of a microencapsulated product involves a number of steps. First, the need for microencapsulation, whether it is to enhance the quality of an existing product or to develop an entirely new product, must be identified. Next, a shell material that provides the desired release characteristics must be chosen. Finally, a process to prepare the microcapsules must be selected.
This procedure is something of an art, as Asajo Kondo asserts in Microcapsule Processing and Technology:
Certain techniques and processes contribute to this view of microencapsulation as an art, primarily because of the broad range of scientific and engineering disciplines they encompass, as well as the interconnectivity of these disciplines.
Consider, for example, the process called complex coacervation. Conceived in the 1930's by colloid chemist Barrett Green at the National Cash Register Corporation, it was the first process used to make microcapsules for carbonless copy paper. In complex coacervation, the substance to be encapsulated is first dispersed as tiny droplets in an aqueous solution of a polymer such as gelatin. For this emulsification process to be successful, the core material must be immiscible in the aqueous phase. Miscibility is assessed using physical chemistry and thermodynamics. The emulsification is usually achieved by mechanical agitation, and the size distribution of the droplets is governed by fluid dynamics.
A second water soluble polymer, such as gum arabic, is then added to this emulsion. After mixing, dilute acetic acid is added to adjust the pH. Though both polymers are soluble in water, addition of the acetic acid results in the spontaneous formation of two incompatible liquid phases. One phase, called the coacervate, has relatively high concentrations of the two polymers; the other phase, called the supernatant, has low polymer concentrations. The concentrations of the polymers in these two phases, and the pH at which phase separation occurs, are governed by specific properties of physical chemistry, thermodynamics, and polymer chemistry.
If the materials are properly chosen, the coacervate preferentially adsorbs onto the surface of the dispersed core droplets, forming microcapsules. Again, physical chemistry and thermodynamics dictate whether the coacervate adsorbs onto the core material. The capsule shells are usually hardened first by cooling (heat transfer), and then by chemical reaction through the addition of a cross-linking agent such as formaldehyde (polymer chemistry). The release characteristics of the microcapsules are governed by materials science (mechanical), heat transport (thermal release), and mass diffusion (diffusion through the wall).
Each aspect of this process is highly dependent upon the others. For example, the thermodynamics of the phase separation affects the composition of the shell material, and this affects the ability of the shell to wet the core phase, as well as determining the barrier properties and release characteristics.
Despite extensive research to fully comprehend the coacervation process, it has been almost impossible to study the influence of each of these factors on an individual basis. Furthermore, answers to some questions how fast should the pH be lowered, how can agglomeration and formation of free coacervates be avoided, what are the effects of rapid cooling remain qualitative.
Considering the difficult questions involved, the interconnectivity of different process elements, and the fact that there are hundreds of encapsulation process variations, it is little wonder that microencapsulation is sometimes regarded as an art. However, at SwRI, researchers are trying to gain a better scientific understanding of the different aspects of chemical and physical encapsulation processes, to more efficiently tailor results to client needs.
Microencapsulation as a Science
Because no single encapsulation process can produce the complete range of products desired by potential users, SwRI has continually expanded its microencapsulation capabilities. In the last 45 years, the Institute has developed and refined a number of microencapsulation processes and devices.
One encapsulation technology used at SwRI for a number of commercial applications is the co-extrusion process.[4,5,6] Liquid core and shell materials are pumped through concentric orifices, with the core material flowing in the central orifice, and the shell material flowing through the outer annulus. A compound drop composed of a droplet of core fluid encased by a layer of shell fluid forms. The shell is then hardened by appropriate means; for example, by chemical crosslinking in the case of polymers, cooling in the case of fats or waxes, or solvent evaporation.
Though it sounds deceptively simple, co-extrusion capsule formation is quite complicated. The size of the capsules produced, as well as the quantity of core material contained within each capsule, depends on the physical properties of the fluids (densities, viscosities, and interfacial tensions), the processing conditions (flowrates and temperatures), the geometry of the nozzle (diameters of the inner and outer orifices), and the amplitude and frequency of small vibrational disturbances (natural or imposed) present in the system. Because there are so many variables, and because it is often difficult to vary one without affecting another (for example, changing the viscosity of the shell fluid changes the interfacial tension between it and the surrounding fluid, and between it and the core fluid), it is extremely difficult to isolate the influence of the individual factors. For this reason, co-extrusion processes are designed, and operating conditions determined, on a case-by-case basis. Nevertheless, the principles of momentum conservation and fluid mechanics relevant to capsule formation processes provide a framework on which Institute researchers are developing a fundamental understanding of capsule formation by co-extrusion.
As discussed, the fluid jet breaks up because of disturbances on the jet surface. The size distribution of the compound drops is related to the frequencies of these disturbances. If the frequency of the disturbance imparted to the jet can be precisely controlled, then a droplet stream with a very narrow size distribution can be produced.
Controlled disturbances can be imparted to jet streams by mechanically shaking the entire nozzle assembly at the desired frequency. However, simply imposing the desired frequency is not sufficient. Forced breakup of a compound fluid jet is a complex process, and the geometry of the compound drops produced is dependent on the imposed frequency.
As disturbances on the jet surface grow, bulges and necks are formed in the jet. Sometimes, the neck of fluid which connects drops just before breakup is not pulled back into one of the droplets, but pinches off at both ends, forming what is termed a satellite droplet. Clearly, if monodisperse drops are desired, satellite formation is unwanted. The mechanisms of, and means to suppress, satellite formation are not well understood and are active areas of fluid mechanics research.[10,11]
Even less is known about compound fluid jets, which exhibit much more complicated behavior. Because there are two fluid jets, the growth rate of disturbance at the shell/air interface can differ from that at the core/shell fluid interface. Satellite droplets can be formed in the shell fluid, resulting in a bimodal distribution of capsule sizes, or in the core fluid, resulting in capsules which have multiple cores.
Because of the multitude of factors that must be taken into account when designing and preparing microcapsules, it is likely that microencapsulation will remain, to some extent, an art. However, this does not preclude a scientific understanding of microencapsulation processes. Researchers at SwRI are working to better understand the physical mechanisms governing compound fluid jet breakup and satellite formation, to design more efficient co-extrusion microencapsulation processes. These processes will be capable of producing capsules with narrower size distributions and more uniform shell thicknesses at higher production rates.
Depending on the flowrates of core and shell materials, capsules are formed in one of two modes: drip or jet. In drip mode, core and shell liquids flow out of the concentric orifices at a low rate, and a compound drop begins to form at the nozzle tip. As is the case with a slowly dripping faucet, surface tension prevents the compound drop from immediately separating from the orifice. However, once it is large enough, the weight of the drop overcomes the cohesive force of surface tension, and the drop falls from the nozzle. As long as the fluid flowrates and temperatures remain constant, this process can produce uniform sized, but fairly large, capsules.
The drip mode co-extrusion process was first used at SwRI in 1949 to encapsulate gasoline for more stable storage, and it is still being used. In 1988, Institute scientists devised a means to encapsulate cells that aid in bone fracture healing. The objective was to find a means to deliver osteoprogenitor cells to the fracture site. Sodium alginate, a known biocompatible substance, was used as the shell material. The core and shell solutions were delivered to a nozzle (a small diameter syringe needle) at a rate of 0.5 milliliter per minute. A stream of air was forced to flow around the needle tip to accelerate the rate of detachment of capsules from the nozzle tip. This resulted in the formation of smaller capsules (approximately 700 microns) compared to the size of those formed without the air stream. The liquid capsules were collected in an aqueous solution of calcium chloride. In this solution, a chemical reaction occurs, in which the water soluble sodium alginate is converted to an insoluble calcium alginate gel.
Although drip mode produces uniform capsules, the production rate is quite low (approximately 20 to 30 capsules per minute). Increased output can only be realized by using multiple nozzles. However, the cost of pumping and capsule collection equipment often prohibits scale-up of drip mode encapsulation processes.
If the flowrates of the core and shell materials are increased beyond some critical value, capsules do not take shape at the nozzle tip. Rather, a compound jet, consisting of a jet of core fluid encased by a sheath of shell fluid, is formed. The critical flowrate is the flowrate at which the inertial force associated with the velocity of the flowing fluid just exceeds the surface tension force, which tends to cause fluid to adhere to the nozzle tip.
A fluid jet is not a stable geometric configuration. Because of surface tension, infinitesimally small perturbations in the jet's shape (from that of a perfectly smooth cylinder) tend to grow, until their size is comparable to the jet diameter. The compound jet breaks up into compound droplets, with diameters roughly twice those of the compound jet.
The jet mode of operation is applied in three different devices at SwRI the stationary nozzle, the rotating centrifugal head, and the submerged nozzle. The stationary nozzle and rotating head are similar in that both extrude capsules into the air. However, in the rotating centrifugal head, multiple nozzles (anywhere from 2 to 50) are mounted on a rotating shaft; thus, capsules are spatially distributed, resulting in fewer capsule agglomeration problems. The submerged nozzle is used to prepare large capsules (greater than one millimeter in diameter) in which the shell is solidified by cooling (air does not provide effective heat transfer for such large particles). The compound fluid jet is extruded into a flowing liquid carrier stream and breakup occurs in this liquid. After the compound drops have formed, the temperature of the liquid carrier fluid is reduced, and the capsule shells solidify.
Centrifugal extrusion has been used at SwRI to prepare encapsulated retinoids, (vitamin A analogs) for use in laboratory animal diets. Encapsulation was necessary because retinoids decompose on exposure to heat, light, and oxygen. A corn oil solution of retinoids was encapsulated in an aqueous gelatin solution and the capsules collected on a bed of starch, which absorbed much of the water from the capsule shell. Head speed and material feed rates were adjusted to obtain capsules in the desired size range.
In a project for the U.S. Bureau of Mines, Institute scientists used the submerged nozzle to prepare water-filled wax capsules for a fast-setting gypsum grouting cement for reinforcing bolt adhesion in coal mine roofs. The water-filled capsules, one to two millimeters in diameter, are mixed with dry gypsum, and the mixture is placed in a thin-walled tube. The tube is then placed in the bolt hole. When the bolt is inserted into the hole, the capsules in the tube are crushed. This releases the water, and the cement rapidly solidifies.
The capsules were prepared by extruding a water/wax compound jet into a conduit through which hot water flowed. Both the core and carrier water temperatures must be high enough so that the jet does not solidify before it breaks into compound drops. Once the drops are formed, the stream is cooled using a double pipe heat exchanger.
The Future of Co-extrusion Processes: Vibration-Assisted Jet Breakup
Though a jet mode of encapsulation yields much higher production rates than a drip mode, capsule uniformity is not as consistent. Standard deviations of capsule sizes are typically 35 to 50 percent of the mean capsule diameter. For many applications, a narrow size distribution, with standard deviations one to two percent of the mean capsule diameter, is desired. Narrow size distributions are of great advantage in applications requiring controlled release. With the ability to control wall thickness and fill quantities, release characteristics of microcapsules can be precisely tailored to specific applications.
Published in the Summer 1995 issue of Technology Today®, published by Southwest Research Institute. For more information, contact Joe Fohn.